A number of diseases or injuries involving bones are known for which repair, regeneration, or augmentation of bone is a desired treatment. Formation of bone in vivo involves an interaction of various inductive proteins which act by causing a differentiation of mesenchymal cells into cartilage and then bone-forming cell lines. This mechanism is not completely understood. However, in efforts to improve orthopedic procedures, purified protein mixtures and recombinantly produced proteins have been developed which stimulate osteoinductive activity.
In general, autogeneous bone grafts have been viewed as the standard for restoring skeletal defects. However, autogeneous sources of bone in human beings are limited, expensive and painful to obtain. Accordingly, materials such as demineralized bone matrix have been developed to augment or replace autogeneous bone grafts. However, an alternative to demineralized bone matrix is desired to improve the ease of use, economy of product manufacture and to eliminate the potential of disease transfer or immune system incompatibilities. To date however, an acceptable substitute has not been identified.
Currently the clinical potential of composite implants containing a mixture of bovine tendon collagen and a proprietary bone morphogenic protein mixture, with demineralized bone matrix powders and simulated body fluid is being evaluated. While a number of advances have improved the activity of osteoinductive factors such as those present in bone morphogenic protein mixtures, their clinical application has been limited, in part, by the requirement for a superior delivery vehicle. Resistance to the use of demineralized bone matrix in certain cultures, as well as the desire to enhance the activity of the bone morphogenic protein mixture to reduce cost, speaks to the desire to develop substitutes for demineralized bone matrix.
The present invention provides compositions that can be used as bone graft substitutes to obtain a product with an improved osteoinductive response for growth factors in degradable implants for skeletal regeneration. The compositions of the present invention are easier to use and more economical to manufacture than demineralized bone matrix, and they eliminate or significantly reduce the potential of both disease and pathogen transfer and immune system incompatibilities.
Numerous materials have been experimentally evaluated as alternative delivery vehicles for osteoinductive growth factors. The materials previously assessed by reconstructive surgeons and scientists include, without limitation, hydroxyapatites, tricalcium phosphates, aliphatic polyesters, cancellous bone allografts, human fibrin, plaster of paris, apatite wollastonite glass ceramics, titanium, devitalized bone matrix, non-collagenous proteins, collagen and autolyzed antigen extracted allogenic bone. None of these materials have been found to be entirely satisfactory.
Other growth factor carriers containing calcium phosphate additives have been developed. For example, a macroporous collagen sponge containing a mixture of a-tricalcium phosphate (α-3CaO.P2O5) and hydroxyapatite (3.33CaO.P2O5(OH)2) has been developed. Alternatively, a macroporous collagen sponge that contains precipitated hydroxyapatite has also been disclosed (U.S. Pat. No. 5,776,193). The composition of such products are consistent with the prevailing view that hydroxyapatite is the preferred calcium phosphate source for bone graft substitutes or extenders due to its compositional similarity with the mineral component of natural bone.
There remains a desire for improved compositions for the induction of bone growth in animals that address the problems of existing compositions and products.